Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparame...Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.展开更多
The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble dif...The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.展开更多
Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It ...Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As t...The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.展开更多
BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatm...BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.展开更多
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho...PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.展开更多
BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link betwee...This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link between H.pylori infection and the development of cholelithiasis through a multicenter retrospective study on an Asian population of over 70000 participants.They also performed a compre-hensive analysis of previously published studies on H.pylori and cholelithiasis,finding a positive association therein[odds ratio(OR)=1.103,P=0.049].Patients positive for H.pylori also had lower levels of total and direct bilirubin,but higher levels of total cholesterol and low-density lipoprotein cholesterol compared to uninfected patients(P<0.05).Cohort studies have confirmed that H.pylori is a risk factor for cholelithiasis(P<0.0001),and aggregate analyses of case-control and cross-sectional studies have shown a positive association between H.pylori and cholelithiasis in Asia(OR=1.599,P=0.034),but not in Europe(OR=1.277,P=0.246).Moreover,H.pylori appears to be related to a higher ratio of choledocho-lithiasis/cholecystolithiasis(OR=3.321,P=0.033).The authors conclude that H.pylori infection is positively correlated with cholelithiasis,particularly with the choledocholithiasis phenotype,especially in Asia,and it is potentially related to bilirubin and cholesterol metabolism.展开更多
Upper gastrointestinal cancers,mainly comprising esophageal and gastric cancers,are among the most prevalent cancers worldwide.There are many new cases of upper gastrointestinal cancers annually,and the survival rate ...Upper gastrointestinal cancers,mainly comprising esophageal and gastric cancers,are among the most prevalent cancers worldwide.There are many new cases of upper gastrointestinal cancers annually,and the survival rate tends to be low.Therefore,timely screening,precise diagnosis,appropriate treatment strategies,and effective prognosis are crucial for patients with upper gastrointestinal cancers.In recent years,an increasing number of studies suggest that artificial intelligence(AI)technology can effectively address clinical tasks related to upper gastrointestinal cancers.These studies mainly focus on four aspects:screening,diagnosis,treatment,and progno-sis.In this review,we focus on the application of AI technology in clinical tasks related to upper gastrointestinal cancers.Firstly,the basic application pipelines of radiomics and deep learning in medical image analysis were introduced.Furthermore,we separately reviewed the application of AI technology in the aforementioned aspects for both esophageal and gastric cancers.Finally,the current limitations and challenges faced in the field of upper gastrointestinal cancers were summarized,and explorations were conducted on the selection of AI algorithms in various scenarios,the popularization of early screening,the clinical applications of AI,and large multimodal models.展开更多
Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histo...Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.展开更多
BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterolo...BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterological questionnaire(PGQ)to assess the psycho-gastroenterological profile and social characteristics of a pediatric population with and without DGBI.METHODS One hundred and nineteen Italian children(age 11-18)were included:28 outpatient patients with DGBI(Rome IV criteria)and 91 healthy controls.They filled the PGQ,faces pain scale revised(FPS-R),Bristol stool chart,ga-strointestinal symptoms rating scale,state-trait anxiety inventory,Toronto alexithymia scale 20,perceived self-efficacy in the management of negative emotions and expression of positive emotions(APEN-G,APEP-G),irritable bowel syndrome-quality of life questionnaire,school performances,tobacco use,early life events,degree of digital-ization.RESULTS Compared to controls,patients had more medical examinations(35%of them went to the doctor more than five times),a higher school performance(23%vs 13%,P<0.05),didn’t use tobacco(never vs 16%,P<0.05),had early life events(28%vs 1%P<0.05)and a higher percentage of pain classified as 4 in the FPS-R during the examination(14%vs 7%,P<0.05).CONCLUSION Pediatric outpatients with DGBI had a higher prevalence of early life events,a lower quality of life,more medical examinations rising health care costs,lower anxiety levels.展开更多
This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a...This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.展开更多
BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis e...BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis evaluation,its application to other abdominal organs,such as the spleen and pancreas,is gaining interest.However,normal stiffness values and inter-system agreement remain poorly defined.AIM To assess the feasibility and agreement of liver,spleen,and pancreas stiffness using three SWE methods.METHODS This single-center observational study enrolled 50 healthy adult volunteers.Liver,spleen,and pancreas stiffness were assessed using three SWE methods:Point-SWE(p-QElaXto)and 2-Dimensional-SWE(2D-QElaXto)with Esaote MyLab 9,and 2D-SWE with SuperSonic Imagine.Feasibility,inter-operator reproducibility,and concordance among systems were evaluated.Stiffness was expressed as median kPa values,and technical reliability was assessed using the interquartile range/median ratio and stability index thresholds.RESULTS Liver and spleen stiffness assessment was feasible in>98%of patients,while pancreas stiffness was measurable in 84%-88%depending on the SWE technique.Mean liver stiffness ranged between 3.9-4.7 kPa across techniques,spleen stiffness ranged from 19.4-23.0 kPa,and pancreas stiffness from 5.2-7.6 kPa.Inter-operator agreement was excellent for liver(intraclass correlation coefficient>0.90)and good to moderate for spleen and pancreas(intraclass correlation coefficient from 0.43 to 0.90).Bland-Altman analysis confirmed good correlation but also systematic differences among devices,especially in pancreas measurements.CONCLUSION This is the first study to establish normal liver,spleen,and pancreas stiffness using MyLab 9 SWE integrated methods as compared to SuperSonic Imagine,with acceptable inter-technique agreement.Liver and spleen values matched existing guidelines;pancreas SWE showed more variability and reduced reproducibility.展开更多
BACKGROUND Endoscopic variceal band ligation(EVBL)represents a pivotal treatment in the prophylaxis of esophageal varices bleeding in patients with cirrhosis,but in some cases a single session of EVBL is unable to era...BACKGROUND Endoscopic variceal band ligation(EVBL)represents a pivotal treatment in the prophylaxis of esophageal varices bleeding in patients with cirrhosis,but in some cases a single session of EVBL is unable to eradicate esophageal varices completely,and a control endoscopy after 2-4 weeks is required to assess eradication and/or the need for another band ligation.Liver stiffness measurement(LSM)is being increasingly used as a screening non-invasive tool to predict varices according to Baveno VII criteria.However,to date,there are no instruments able to non-invasively predict the outcome of EVBL.AIM To identify non-invasive predictors of varices eradication(VE)after EVBL through multiparametric ultrasound(US).Secondary aim was to develop a prediction model of successful variceal eradication based on non-invasive parameters.METHODS We prospectively enrolled consecutive cirrhotic patients intolerant or with contraindications to beta-blockers undergoing EVBL for bleeding prophylaxis.Patients underwent multiparametric US with LSM,spleen stiffness measurement(SSM)and dynamic contrastenhanced US(DCE-US)on liver parenchyma and portal vein,at baseline(T0)and one month(T1)after EVBL.Each US parameter and their variations from baseline were correlated with VE evaluated by control endoscopy performed at T1.RESULTS We enrolled 41 patients(median age 64 years,75.6%males).At T128 patients(68.3%)reached VE,whereas 13(31.7%)required a second EVBL.Patients who achieved VE showed a significant decrease in SSM(P=0.018),and a significant increase in peak enhancement,area under the curve and wash-in rate of both liver parenchyma and portal vein after treatment(P<0.001).Statistically significant differences between the two groups of patients were incorporated in a multivariate analysis and used to develop three prediction models.CONCLUSION A multimodal US approach based on DCE-US parameters,LSM and SSM might become a reliable predictor of VE and a useful non-invasive alternative to endoscopy.展开更多
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
文摘Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.
基金supported by FATALSDrug Project [Progetti di Ricerca@CNR SAC.AD002.173.058] from National Research Council,Italy (to CV)。
文摘The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金supported by Italian Ministry of Health Ricerca Corrente [RC 2023] and RF-2016-02361294supported by#NEXTGENERATIONEU (NGEU)+3 种基金funded by the Ministry of University and Research (MUR)National Recovery and Resilience Plan (NRRP)project MNESYS (PE0000006)–A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022)(to FRG)partially supported by a grant from Fondazione Romeo ed Enrica Invernizzi (to FRG)。
文摘Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
文摘The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.
文摘BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.
基金supported by Telethon Italy award GGP15225(to RC and GM)Italian Ministry of Health award RF-2016-02362950(to RC and CZ)+1 种基金the CJD Foundation USA(to RC)the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).
文摘PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
文摘This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link between H.pylori infection and the development of cholelithiasis through a multicenter retrospective study on an Asian population of over 70000 participants.They also performed a compre-hensive analysis of previously published studies on H.pylori and cholelithiasis,finding a positive association therein[odds ratio(OR)=1.103,P=0.049].Patients positive for H.pylori also had lower levels of total and direct bilirubin,but higher levels of total cholesterol and low-density lipoprotein cholesterol compared to uninfected patients(P<0.05).Cohort studies have confirmed that H.pylori is a risk factor for cholelithiasis(P<0.0001),and aggregate analyses of case-control and cross-sectional studies have shown a positive association between H.pylori and cholelithiasis in Asia(OR=1.599,P=0.034),but not in Europe(OR=1.277,P=0.246).Moreover,H.pylori appears to be related to a higher ratio of choledocho-lithiasis/cholecystolithiasis(OR=3.321,P=0.033).The authors conclude that H.pylori infection is positively correlated with cholelithiasis,particularly with the choledocholithiasis phenotype,especially in Asia,and it is potentially related to bilirubin and cholesterol metabolism.
基金supported by the National Key R&D Program of China(grant number:2023YFC2415200)National Natural Science Foundation of China(grant numbers:82361168664,U24A20759,82441018,82372053,92259302,62027901,82302296)+6 种基金Science and Technology Development Fund of Macao Special Administrative Region(grant number:0006/2023/AFJ)Strategic Priority Research Program of the Chinese Academy of Sciences(grant number:XDB38040200)Beijing Natural Science Foundation(grant numbers:Z20J00105,JQ24048)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(grant number:CI2023C008YG)Key-Area Re-search and Development Program of Guangdong Province(grant number:2021B0101420005)the Youth Innovation Promotion Association CAS(grant number:Y2021049)China Postdoctoral Science Foun-dation under Grant(grant number:2022M720357)。
文摘Upper gastrointestinal cancers,mainly comprising esophageal and gastric cancers,are among the most prevalent cancers worldwide.There are many new cases of upper gastrointestinal cancers annually,and the survival rate tends to be low.Therefore,timely screening,precise diagnosis,appropriate treatment strategies,and effective prognosis are crucial for patients with upper gastrointestinal cancers.In recent years,an increasing number of studies suggest that artificial intelligence(AI)technology can effectively address clinical tasks related to upper gastrointestinal cancers.These studies mainly focus on four aspects:screening,diagnosis,treatment,and progno-sis.In this review,we focus on the application of AI technology in clinical tasks related to upper gastrointestinal cancers.Firstly,the basic application pipelines of radiomics and deep learning in medical image analysis were introduced.Furthermore,we separately reviewed the application of AI technology in the aforementioned aspects for both esophageal and gastric cancers.Finally,the current limitations and challenges faced in the field of upper gastrointestinal cancers were summarized,and explorations were conducted on the selection of AI algorithms in various scenarios,the popularization of early screening,the clinical applications of AI,and large multimodal models.
基金supported by an under-40 grant from the Italian Association for Alzheimer’s Research [AIRALZH AGYR2021]the Strategic University Projects–Young Researcher Independence grant [YRG2021] from the Università Campus Bio-Medico di Roma (Rome, Italy)(to LLB)+1 种基金Italian Ministry of Health [Research Grant:GR-2019-12370446]the American Alzheimer’s Association [AARG-22-922961](to PK)。
文摘Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.
文摘BACKGROUND Disorders of gut-brain interaction(DGBI)are common,but knowledge about their physiopathology is still poor,nor valid tools have been used to evaluate them in childhood.AIM To develop a psycho-gastroenterological questionnaire(PGQ)to assess the psycho-gastroenterological profile and social characteristics of a pediatric population with and without DGBI.METHODS One hundred and nineteen Italian children(age 11-18)were included:28 outpatient patients with DGBI(Rome IV criteria)and 91 healthy controls.They filled the PGQ,faces pain scale revised(FPS-R),Bristol stool chart,ga-strointestinal symptoms rating scale,state-trait anxiety inventory,Toronto alexithymia scale 20,perceived self-efficacy in the management of negative emotions and expression of positive emotions(APEN-G,APEP-G),irritable bowel syndrome-quality of life questionnaire,school performances,tobacco use,early life events,degree of digital-ization.RESULTS Compared to controls,patients had more medical examinations(35%of them went to the doctor more than five times),a higher school performance(23%vs 13%,P<0.05),didn’t use tobacco(never vs 16%,P<0.05),had early life events(28%vs 1%P<0.05)and a higher percentage of pain classified as 4 in the FPS-R during the examination(14%vs 7%,P<0.05).CONCLUSION Pediatric outpatients with DGBI had a higher prevalence of early life events,a lower quality of life,more medical examinations rising health care costs,lower anxiety levels.
文摘This editorial is a commentary on the case report by Furuya et al focusing on the challenging diagnosis of early pancreatic adenocarcinoma and new tools for an earlier diagnosis.Currently,pancreatic cancer still has a poor prognosis,mainly due to late diagnosis in an advanced stage.Two main precancerous routes have been identified as pathways to pancreatic adenocarcinoma:The first encompasses a large group of mucinous cystic lesions:intraductal papillary mucinous neoplasm and mucinous cystic neoplasm,and the second is pancreatic intraepithelial neoplasia.In the last decade the focus of research has been to identify high-risk patients,using advanced imaging techniques(magnetic resonance cholangiopancreatography or endoscopic ultrasonography)which could be helpful in finding“indirect signs”of early stage pancreatic lesions.Nevertheless,the survival rate still remains poor,and alternative screening methods are under investigation.Endoscopic retrograde cholangiopancreatography followed by serial pancreatic juice aspiration cytology could be a promising tool for identifying precursor lesions such as intraductal papillary mucinous neoplasm,but confirming data are still needed to validate its role.Probably a combination of cross-sectional imaging,endoscopic techniques(old and new ones)and genetic and biological biomarkers also in pancreatic juice)could be the best solution to reach an early diagnosis.Biomarkers could help to predict and follow the progression of early pancreatic lesions.However,further studies are needed to validate their diagnostic reliability and to establish diagnostic algorithms to improve prognosis and survival in patients with pancreatic cancer.
文摘BACKGROUND Shear wave elastography(SWE)is a non-invasive ultrasound-based technique used to assess tissue stiffness,which reflects underlying pathological changes.While SWE has been widely applied for liver fibrosis evaluation,its application to other abdominal organs,such as the spleen and pancreas,is gaining interest.However,normal stiffness values and inter-system agreement remain poorly defined.AIM To assess the feasibility and agreement of liver,spleen,and pancreas stiffness using three SWE methods.METHODS This single-center observational study enrolled 50 healthy adult volunteers.Liver,spleen,and pancreas stiffness were assessed using three SWE methods:Point-SWE(p-QElaXto)and 2-Dimensional-SWE(2D-QElaXto)with Esaote MyLab 9,and 2D-SWE with SuperSonic Imagine.Feasibility,inter-operator reproducibility,and concordance among systems were evaluated.Stiffness was expressed as median kPa values,and technical reliability was assessed using the interquartile range/median ratio and stability index thresholds.RESULTS Liver and spleen stiffness assessment was feasible in>98%of patients,while pancreas stiffness was measurable in 84%-88%depending on the SWE technique.Mean liver stiffness ranged between 3.9-4.7 kPa across techniques,spleen stiffness ranged from 19.4-23.0 kPa,and pancreas stiffness from 5.2-7.6 kPa.Inter-operator agreement was excellent for liver(intraclass correlation coefficient>0.90)and good to moderate for spleen and pancreas(intraclass correlation coefficient from 0.43 to 0.90).Bland-Altman analysis confirmed good correlation but also systematic differences among devices,especially in pancreas measurements.CONCLUSION This is the first study to establish normal liver,spleen,and pancreas stiffness using MyLab 9 SWE integrated methods as compared to SuperSonic Imagine,with acceptable inter-technique agreement.Liver and spleen values matched existing guidelines;pancreas SWE showed more variability and reduced reproducibility.
文摘BACKGROUND Endoscopic variceal band ligation(EVBL)represents a pivotal treatment in the prophylaxis of esophageal varices bleeding in patients with cirrhosis,but in some cases a single session of EVBL is unable to eradicate esophageal varices completely,and a control endoscopy after 2-4 weeks is required to assess eradication and/or the need for another band ligation.Liver stiffness measurement(LSM)is being increasingly used as a screening non-invasive tool to predict varices according to Baveno VII criteria.However,to date,there are no instruments able to non-invasively predict the outcome of EVBL.AIM To identify non-invasive predictors of varices eradication(VE)after EVBL through multiparametric ultrasound(US).Secondary aim was to develop a prediction model of successful variceal eradication based on non-invasive parameters.METHODS We prospectively enrolled consecutive cirrhotic patients intolerant or with contraindications to beta-blockers undergoing EVBL for bleeding prophylaxis.Patients underwent multiparametric US with LSM,spleen stiffness measurement(SSM)and dynamic contrastenhanced US(DCE-US)on liver parenchyma and portal vein,at baseline(T0)and one month(T1)after EVBL.Each US parameter and their variations from baseline were correlated with VE evaluated by control endoscopy performed at T1.RESULTS We enrolled 41 patients(median age 64 years,75.6%males).At T128 patients(68.3%)reached VE,whereas 13(31.7%)required a second EVBL.Patients who achieved VE showed a significant decrease in SSM(P=0.018),and a significant increase in peak enhancement,area under the curve and wash-in rate of both liver parenchyma and portal vein after treatment(P<0.001).Statistically significant differences between the two groups of patients were incorporated in a multivariate analysis and used to develop three prediction models.CONCLUSION A multimodal US approach based on DCE-US parameters,LSM and SSM might become a reliable predictor of VE and a useful non-invasive alternative to endoscopy.
